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[0] Suner S, Fellows MR, Vargas-Irwin C, Nakata GK, Donoghue JP, Reliability of signals from a chronically implanted, silicon-based electrode array in non-human primate primary motor cortex.IEEE Trans Neural Syst Rehabil Eng 13:4, 524-41 (2005 Dec)

[0] Westby GW, Wang H, A floating microwire technique for multichannel chronic neural recording and stimulation in the awake freely moving rat.J Neurosci Methods 76:2, 123-33 (1997 Oct 3)

[0] Rousche PJ, Normann RA, Chronic recording capability of the Utah Intracortical Electrode Array in cat sensory cortex.J Neurosci Methods 82:1, 1-15 (1998 Jul 1)

[0] Kipke DR, Vetter RJ, Williams JC, Hetke JF, Silicon-substrate intracortical microelectrode arrays for long-term recording of neuronal spike activity in cerebral cortex.IEEE Trans Neural Syst Rehabil Eng 11:2, 151-5 (2003 Jun)

[0] Porada I, Bondar I, Spatz WB, Kruger J, Rabbit and monkey visual cortex: more than a year of recording with up to 64 microelectrodes.J Neurosci Methods 95:1, 13-28 (2000 Jan 31)

[0] Schmidt EM, Single neuron recording from motor cortex as a possible source of signals for control of external devices.Ann Biomed Eng 8:4-6, 339-49 (1980)[1] Schmidt EM, McIntosh JS, Durelli L, Bak MJ, Fine control of operantly conditioned firing patterns of cortical neurons.Exp Neurol 61:2, 349-69 (1978 Sep 1)[2] Salcman M, Bak MJ, A new chronic recording intracortical microelectrode.Med Biol Eng 14:1, 42-50 (1976 Jan)

[0] Nicolelis MA, Dimitrov D, Carmena JM, Crist R, Lehew G, Kralik JD, Wise SP, Chronic, multisite, multielectrode recordings in macaque monkeys.Proc Natl Acad Sci U S A 100:19, 11041-6 (2003 Sep 16)

[0] Csicsvari J, Henze DA, Jamieson B, Harris KD, Sirota A, Bartho P, Wise KD, Buzsaki G, Massively parallel recording of unit and local field potentials with silicon-based electrodes.J Neurophysiol 90:2, 1314-23 (2003 Aug)

[0] Williams JC, Rennaker RL, Kipke DR, Long-term neural recording characteristics of wire microelectrode arrays implanted in cerebral cortex.Brain Res Brain Res Protoc 4:3, 303-13 (1999 Dec)

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ref: Seymour-2007.09 tags: neural probe design recording Kipke Seymour parelene MEA histology PEDOT date: 02-23-2017 23:52 gmt revision:13 [12] [11] [10] [9] [8] [7] [head]

PMID-17517431[0] Neural probe design for reduced tissue encapsulation in CNS.

  • See conference proceedings too: PMID-17947102[1] Fabrication of polymer neural probes with sub-cellular features for reduced tissue encapsulation.
    • -- useful information.
  • They use SU8 - photoresist! - as a structural material. See also this.
    • They use silicon as a substrate for the fabrication, but ultimately remove it. Electrodes could be made of titanium, modulo low conductivity.
  • Did not / could not record from these devices. Only immunochemistry.
  • Polymer fibers smaller than 7um are basically invisible to the immune system. See [2]
  • Their peripheral recording site is 4 x 5um - but still not invisible to microglia. Perhaps this is because of residual insertion trauma, or movement trauma? They implanted the device flush with the cortical surface, so there should have been little cranial tethering.
  • Checked the animals 4 weeks after implantation.
  • Peripheral electrode site was better than shank location, but still not perfect. Well, any improvement is a good one...
  • No statistical difference between 4x5um lattice probes, 10x4um probes, 30x4um, and solid (100um) knife edge.
    • Think that this may be because of electrode micromotion -- the lateral edge sites are still relatively well connected to the thick, rigid shank.
  • Observed two classes of immune reactivity --
    • GFAP reactive hypertrophied astrocytes.
    • devoid of GFAP, neurofilament, and NEuN, but always OX-42 and often firbronectin and laminin positive as well.
    • Think that the second may be from meningeal cells pulled in with the stab wound.
  • Sensitivity is expected to increase with decreased surface area (but similar low impedance -- platinum black or oxidized iridium or PEDOT {1112} ).
  • Thoughts: it may be possible to put 'barbs' to relieve mechanical stress slightly after the probe location, preferably spikes that expand after implantation.
  • His thesis {1110}

____References____

[0] Seymour JP, Kipke DR, Neural probe design for reduced tissue encapsulation in CNS.Biomaterials 28:25, 3594-607 (2007 Sep)
[1] Seymour JP, Kipke DR, Fabrication of polymer neural probes with sub-cellular features for reduced tissue encapsulation.Conf Proc IEEE Eng Med Biol Soc 1no Issue 4606-9 (2006)
[2] Sanders JE, Stiles CE, Hayes CL, Tissue response to single-polymer fibers of varying diameters: evaluation of fibrous encapsulation and macrophage density.J Biomed Mater Res 52:1, 231-7 (2000 Oct)

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ref: -0 tags: iridium oxide nanotube intracellular recording electroplate MEA date: 02-22-2017 22:41 gmt revision:0 [head]

PMID-24487777 Iridium oxide nanotube electrodes for sensitive and prolonged intracellular measurement of action potentials.

  • Electrodeposition of IrOx "magically" forms 500nm tubes.
  • Holes in Si3N4 / SiO2 were formed via e-beam lithography; underlying Pt wires via liftoff.
  • Showed long (minutes) intracellular access, though it tended to dip with time.

{1367}
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ref: -0 tags: microstimulation rat cortex measurement ICMS spread date: 01-26-2017 02:52 gmt revision:0 [head]

PMID-12878710 Spatiotemporal effects of microstimulation in rat neocortex: a parametric study using multielectrode recordings.

  • Measure using extracellular ephys a spread of ~ 1.3mm from near-threshold microstimulation.
  • Study seems thorough despite limited techniques.

{1337}
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ref: -0 tags: molecule mean free path vacuum date: 05-01-2016 03:16 gmt revision:0 [head]

Useful numbers for estimating molecular mean-free-path in vacuum systems:

"

PressureTorrMean free path
0.01 Pa7.5e-5 torr4.8 m
10 Pa75 mTorr4.8 mm
30 Pa225 mTorr1.6 mm

{1060}
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ref: -0 tags: electrode carbon fiber MEA date: 04-22-2013 18:19 gmt revision:2 [1] [0] [head]

PMID-21228307 Ultrasmall and customizable multichannel electrodes for extracellular recordings

  • 7um carbon fiber electrodes.
  • It has been estimated that insertion of a 50 um wire in the adult rat hippocampus CA1 area could damage 90% of the neurons that would otherwise be recordable by the electrode (Claverol-Tinture and Nadasdy 2004)
  • Highlight the tetrode effect: it's like beam forming.
  • Carbon fibers from Goodfellow Cambridge.
  • Insulated with a pulled micropipette.
  • Added insulation with cathodic electrodeposition paint (Claerclad HSR)
  • focused ion beam milling (FIB) (Qiao et al 2005) -- working resolution below 10nm.
  • The carbon fibers were fond to be stiff enough to penetrate the fly 'dura'.

{597}
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ref: Suner-2005.12 tags: Suner Utah probe electrophysiology reliability chronic electrode recording longevity histology MEA date: 01-31-2013 22:27 gmt revision:7 [6] [5] [4] [3] [2] [1] [head]

PMID-16425835Reliability of signals from a chronically implanted, silicon-based electrode array in non-human primate primary motor cortex

  • claim that they have done a logitudinal development series that included 39 array implants in 18 monkeys.
  • can get reliable recordings out to 3 months (only? probably the array was forced out of the brain?)
    • however, it seems that their recording quality did not decrease dramatically over those 3 months.
  • excellent methods section.
  • also {1027}

____References____

{999}
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ref: -0 tags: microelectrodes original metal pipette glass recording MEA date: 01-31-2013 19:46 gmt revision:6 [5] [4] [3] [2] [1] [0] [head]

IEEE-4065599 (pdf) Comments on Microelectrodes

  • The amplifiers themselves, even back in 1950's, posed no problems -- low bandwidth. All that is required is low noise and high input impedance.
  • KCl Glass electrodes are LPF (10M resistive + 10pf parasitic capacitance); metal HPF (capacitive).
    • The fluid tip will not see external triphasic spikes of vertebrate axons above the noise level.
  • Metal probe the most useful.
  • Pt electrode in CSF behaves like a capacitor at low voltage across a broad frequency range. CSF has compounds that retard oxidation; impedance is more resistive with physiological saline.
  • Noise voltage generated by a metal electrode best specified by equivalent noise resistance at room temperature, E rmsnoise=4kTR nδF R_n should equal the real part of the electrode impedance at the same frequency.
  • Much of electrochemistry: solid AgCl diffuses away from an electrode tip with great speed and can hardly be continuously formed with an imposed current. Silver forms extremely stable complexes with organic molecules having attached amino and sulfhydril groups which occur in plenty where the electrode damages the tissue. Finally, the reduction-oxidation potential of axoplasm is low enough to reduce methylene blue, which places it below hydrogen. AgCl and HgCl are reduced.
  • The external current of nerve fibers is the second derivative of the traveling spike, the familiar triphasic (??) transient.
  • Svaetichin [1] and Dowben and Rose [3] plated with Platinum black. This increases the surface area.
    • Very quickly it burns onto itself a shell of very adherent stuff. It is kept from intimate contact with the tissue around it by a shell.
    • We found that if we add gelatin to the chloroplatinic acid bath from which we plate the Pt, the ball is not only made adherent to the tip but is, in a sense, prepoisoned and does not burn a shell into itself.
  • glass insulation using woods metal (which melts at a very low temperature). Platinum ball was plated onto 2-3um pipette tip. 3um gelatinized platinum black ball, impedance 100kOhm at 1kHz.
    • Highly capacitive probe: can be biased to 1 volt by a polarizing current of 1e-10 amp. (0.1nA).
  • Getting KCl solution into 1um pipettes is quite hard! They advise vacuum boiling to remove the air bubbles.
  • Humble authors, informative paper.

____References____

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{823}
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ref: Kruger-2010.05 tags: microelectrode array nichrome 7 years rhesus electrophysiology MEA Kruger oblique inverted date: 01-29-2013 07:54 gmt revision:7 [6] [5] [4] [3] [2] [1] [head]

PMID-20577628[0] Seven years of recording from monkey cortex with a chronically implanted multiple electrode.

  • Seven years!! good recordings the whole time, too. As they say, this is a clinically realistic time period. Have they solved the problem?
  • Used 12.5um Ni-Cr-Al wire insulated with 3um of polymide.
    • Wires were then glued to an 8x8 connector block using conductive epoxy.
    • Glued the bundle together with a solution of plexiglas in dichloroethane.
    • Then introduced the 0.3mm bundle into a j-shaped cannula. This allowed them to approach the gray matter inverted, from below (the white matter).
    • implanted 64 ch array into ventral premotor cortex (arm representation?).
  • No apparent degradation of recording quality over that time.
  • Had some serious problems with the quality of their connector.
    • They recommend: "Rather, the contacts on the head should be made from noble metals and be flat or shallowly hollow, so that they can be easily cleaned, and no male contacts can break."
    • Really need to amplify and multiplex prior connector (imho).
  • Claim that them managed to record from two neurons on one channel for nearly 7 years (ch 54).
  • They cite us, but only to indicate that we recommend slow penetration of the brain. They agree with our results that lowering of individual electrodes is better than all at once.

____References____

[0] Kruger J, Caruana F, Volta RD, Rizzolatti G, Seven years of recording from monkey cortex with a chronically implanted multiple microelectrode.Front Neuroengineering 3 Issue 6 (2010 May 28)

{946}
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ref: Salcman-1976.01 tags: Salcman electrodes recording chronic microelectrode array MEA original parylene date: 01-28-2013 22:18 gmt revision:8 [7] [6] [5] [4] [3] [2] [head]

PMID-1256090[0] A new chronic recording intracortical microelectrode

  • maintain that tethering is the rational way to go: it "re-establishes the normal biomechanics of the intact cranial vault". (Salcman 1972, 1973) {1010}
    • have model of electrode tip motion in response to brain-skull displacements (Goldstein and Salcman 1973) {1011}
      • Electrode would have a tip displacement of about 5um in response to a 1mm displacement of the electrode's point of entry into the skull.
      • Exponential dependence on recording amplitude and distance (Rall, 1962). Gradient: 7.5uv/um; movements of more than 1-2um can radically alter the recordnig shape.
      • Probably our electrodes work because the dura & gliosis becomes firmly attached to the electrode shafts.
    • not really an array so much as a number (10-12) of single-unit electrodes.
  • Details the process of parylene-C deposition, electrode microwelding, etc. Pretty cool stuff -- what has happened to this technology?
  • Each bubble is glued with cyanocrylate to the pia. (they too question the safety of this).
  • arrays can be manually inserted via forceps.
  • 25um iridium wire electroplated in 1-2um of gold
    • then electo-etched until the desired tip geometry is achieved, 1-3um diameter
    • and vacuum coated in 3um of parylene-C.
    • Impedance 1-2M with a 1kHz sine wave at 10nA. Impedance is inversely related to the frequency of the test current, phase angle of 70-80deg.
      • Ref Robinson, 1968.
    • We must emphasize the extreme sensitivity of electrode measurements to the test conditions. Measured values of Z e are usually increased 1-3M when the electrode has been stored away for a few days. Removing the electrode from the test bath for a few minutes in air can lead to equally large increases when the electrode is tested upon remersion. [...] might be oxide.
    • Pinholes are the usual failure mechanism (KD Wise 2004), {149}; parylene is 'pinhole-free'.
  • The connecting 25um Au lead is very flexible and imposes little stress on the iridium electrode.
    • Connecting wire coated in 12um of parylene C
    • Would prefer even finer wire, 12um.
  • Perspex window over the craniotomy; had a vent in this window which they could open.
  • Opening the vent would cause the brain to pulse, moving the electrodes through the cortex and changing neural activity.
  • Size of an electrode is limited by ability to introduce it into the brain.
    • Electrode must be introduced through the pia; as the pial vessels supply the cortex (or drain the cortex).
    • For their electrodes, P crit=0.9g ; the force necessary to penetrate the pia is 0.05 - 0.2g.
  • pure iridium is stiffer than Pt-Ir by a factor of 3 or so. (521 G N/m^2 = 521 GPa, higher than tungsten, which is 400 Gpa)
    • Pure iridium is apparently the stiffest metallic element ref
  • Interesting: "Once again we are impressed by the fact that passive recording electrodes exhibit drops in impedance in the living system which they never show on in vitro testing in protein solutions at 37C.
    • Between 40 and 50 days, a slow downward trend becomes noticeable; this trend continues for the life of the animal and asymptotically approaches values below 500k. Electrodes still record.
    • See {999}
    • Surmise that pure iridium electrodes have a different metal-electrolyte interface than more conventional metals (Pl and W).
  • Mention that the ultimate purpose is for a neural prosthesis.
    • Their then use was for recordings from M1 in monkeys and V1 from cats. (Schmidt, Bak, McIntosh 1974)
  • Ref Wise et al {1012}.

____References____

[0] Salcman M, Bak MJ, A new chronic recording intracortical microelectrode.Med Biol Eng 14:1, 42-50 (1976 Jan)

{748}
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ref: Leung-2008.08 tags: biocompatibility alginate tissue response immunochemistry microglia insulation spin coating Tresco recording histology MEA date: 01-28-2013 21:19 gmt revision:4 [3] [2] [1] [0] [head]

PMID-18485471[0] Characterization of microglial attachment and cytokine release on biomaterials of differing surface chemistry

  • The important result is that materials with low protein-binding (e.g. alginate) have fewer bound microglia, hence better biocompatibility. It also seems to help if the material is highly hydrophilic.
    • Yes alginate is made from algae.
  • Used Michigan probes for implantation.
  • ED1 = pan-macrophage marker.
    • (quote:) Quantification of cells on the surface indicated that the number of adherent microglia appeared higher on the smooth side of the electrode compared to the grooved, recording site side (Fig. 2B), and declined with time. However, at no point were electrodes completely free of attached and activated microglial cells nor did these cells disappear from the interfacial zone along the electrode tract.
    • but these were not coated with anything new .. ???

____References____

[0] Leung BK, Biran R, Underwood CJ, Tresco PA, Characterization of microglial attachment and cytokine release on biomaterials of differing surface chemistry.Biomaterials 29:23, 3289-97 (2008 Aug)

{1028}
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ref: Szarowski-2003.09 tags: Michigan array silicon histology MEA cornell date: 01-28-2013 20:47 gmt revision:6 [5] [4] [3] [2] [1] [0] [head]

PMID-12914963[0] Brain responses to micro-machined silicon devices.

  • Used 2 different implants (rough & sharp corners, smooth), 2 different ways of inserting (slow, by hand).
    • Neither made much diff.
  • Measured GFAP = glial fibrillary acidic protein, a standard measure for assesing reactive gliosis [44,18,28,33,35].
    • Normally larger astrocytes were seen around larger blood vessels.
    • "At four weeks, a clear sheath of GFAP-positive astrocytes was observed"
    • GFAP labeled sheath seems to have plateaued at 6 weeks. (The sheath may be useful for our devices... )
  • Measured Vimentin, which is increased in reactive astrocytes and is not normally expressed in mature astrocytes [6,12,15,40].
    • In control animals vimentin only present in ependymal lining of the ventricles.
    • At 6 weeks, sites around both types of devices had a compact sheath of vimentin-positive astrocytes 50-100um.
    • Seemed to be a plateau as with GFAP .. though it seems to label a slightly distinct set of cells.
  • Also labeled reactive microglia with ED1 [4,19,27,36].
  • Quote: These data indicate that device insertion promotes two responses-an early response that is proportional to device size and a sustained response that is independent of device size, geometry, and surface roughness. The early response may be associated with the amount of damage generated during insertion. The sustained response is more likely due to tissue-device interactions.

____References____

[0] Szarowski DH, Andersen MD, Retterer S, Spence AJ, Isaacson M, Craighead HG, Turner JN, Shain W, Brain responses to micro-machined silicon devices.Brain Res 983:1-2, 23-35 (2003 Sep 5)

{895}
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ref: XindongLiu-2006.03 tags: neural recording electrodes stability cat parlene McCreery MEA date: 01-28-2013 02:50 gmt revision:7 [6] [5] [4] [3] [2] [1] [head]

IEEE-1605268 (pdf) Evaluation of the Stability of Intracortical Microelectrode Arrays

  • 35-50um IR electrodes, electrolytically sharpened at a 10 deg angle, with a 5um blunted tip.
  • Electrodes coated in parylene, and exposed at the tip with an eximer laser. Surface area of tip ~500um^2.
  • Sorted based on features (duration, pk-pk, ratio of + to -, ratio of + time to - time), followed by a demixing matrix (PCA?)
  • Did experiments in 25 cats with some task (for another paper?); got recordings for up to 800 days. Seems consistent with our results.
  • Neurons were stable (by their metrics) for up to 60 days.
  • sparse arrays showed stable recordings sooner than dense arrays, perhaps because they are larger and more qucikly become attached to the dura.
  • Electrodes were always unstable for the first 2-3 months. Stability index is as high as 30-40 days.
  • Average electrode yield was ~ 25%.
  • no histology.

____References____

Xindong Liu and McCreery, D.B. and Bullara, L.A. and Agnew, W.F. Evaluation of the stability of intracortical microelectrode arrays Neural Systems and Rehabilitation Engineering, IEEE Transactions on 14 1 91 -100 (2006)

{1010}
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ref: Salcman-1973.07 tags: Salcman MEA microelectrodes chronic recording glass cyanocrylate date: 01-28-2013 02:37 gmt revision:6 [5] [4] [3] [2] [1] [0] [head]

IEEE-4120641 (pdf) Design, Fabrication, and In Vivo Behavior of Chronic Recording Intracortical Microelectrodes

  • Teflon-coated 25um Pt-Ir (90/10)
  • Heat fuse this with a glass micropipette & backfill with cyanoacrylate. {1011}
    • Isobutyl acrylate is hydrolysed more slowly and hence is less toxic to the surronding tissue
    • cyanoacrylate is apparently biodegradable.
  • Durable, stable: one electrode displayed a single cortical spike (though not necessarily the same one) for more than 90 consecutive days.
  • unacceptably low impedance = 100K or less
  • Unit activity was present only 10-24H after surgery.
  • formal review of even older microelectrode studies.
  • 10nA should be 100x too small to have any effect on a platinum tip [17]
  • A seperable cell with a SNR of 3:1 would become lost if the electrode tip moved 15um away from a 20um soma.
    • "It becomes clear that the problem of holding single units for prolonged periods in the unrestrained animal is not achieved without considerable difficulty". Yet they think they have solved it.

____References____

Salcman, Michael and Bak, Martin J. Design, Fabrication, and In Vivo Behavior of Chronic Recording Intracortical Microelectrodes Biomedical Engineering, IEEE Transactions on BME-20 4 253 -260 (1973)

{898}
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ref: Ward-2009.07 tags: microelectrode arrays immune response recording MEA Purdue date: 01-28-2013 01:52 gmt revision:8 [7] [6] [5] [4] [3] [2] [head]

PMID-19486899[0] Toward a comparison of microelectrodes for acute and chronic recordings.

  • Good research, paper well written.
  • Results suggest significant variability within and between microelectrode types with no clearly superior array (from the abstract).
  • As Miguel mantains, "Much of the new technology, however, does not supersede traditional microwire technology in its ability to evade a host immune response".
  • Initial implantation wound initiates a cascade of immune responses which culminates in a sheath of microglia, astrocytes, various ectracellular matrix constituents, and macrophages.
    • Decent citation list -- many people have been working on MEAs.
  • Fibrous encapusulation of the electrode is much less conductive than healthy nervous tissue, hence impedance measurements can be used to track tissue response.
  • Used Osort to sort the recorded neurons.
  • "Despite differing implant locations, and thus potentially differing levels of background neural activity, and differing scarring responses, which relates to the level of thermal noise in the observed signal (Ludwig et al., 2006), no significant SNR differences were observed among the MEA types for the duration of the study."
  • SNR trends did not seem to relate to site impedance trends over the 31-day period, and by inference, the extent of tissue encapsulation and neuronal density loss.
    • SNR is likely controlled by background neural noise, not thermal noise (which would be linked to impedance).
  • Electrodes with lower impedance generally recorded units from more sites than arrays with higher impedance.

____References____

[0] Ward MP, Rajdev P, Ellison C, Irazoqui PP, Toward a comparison of microelectrodes for acute and chronic recordings.Brain Res 1282no Issue 183-200 (2009 Jul 28)

{78}
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ref: Musallam-2007.02 tags: Musallam MEA floating rats electrodes date: 01-28-2013 00:42 gmt revision:7 [6] [5] [4] [3] [2] [1] [head]

PMID-17067683[0] A floating metal microelectrode array for chronic implantation

  • Cite Gualtierotti and Bailey (1968) for a neutral-boyancy electrode w/ rigid shaft.
  • Alumina ceramic base, laser drilled.
  • insulated with silane follwed by parylene-C, 3um.
  • Tips exposed by eximer laser. (Schmidt et al, 1995)
  • Electrophysiology, but not histology.
  • Earlier conference proceedings: PMID-17946982[1] Active floating micro electrode arrays (AFMA).

____References____

[0] Musallam S, Bak MJ, Troyk PR, Andersen RA, A floating metal microelectrode array for chronic implantation.J Neurosci Methods 160:1, 122-7 (2007 Feb 15)
[1] Kim T, Troyk PR, Bak M, Active floating micro electrode arrays (AFMA).Conf Proc IEEE Eng Med Biol Soc 1no Issue 2807-10 (2006)

{311}
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ref: Westby-1997.1 tags: recording microwire electrode MEA sweet sucrose saliva dissolving FET floating date: 01-28-2013 00:28 gmt revision:5 [4] [3] [2] [1] [0] [head]

PMID-9350963 A floating microwire technique for multichannel neural recording and stimulation in the awake rat

  • sweet electrodes -- attached to glass micropipette with sucrose or saliva.
    • Chorover and DeLuca 1972 "A sweet new multiple electrode for chronic single unit recording". {1019}
  • 42 implanted rats, 252 implanted wires, 79% yield. 62% of electrodes still working at 5 weeks.
    • Targeting an area with really large somas (50um).
  • fully-floating 25um microwire ellectrodes.
  • platinum iridium, 25um, teflon coated, handled only with silastic-protected pliers & tweezers to prevent damage to the insulation.
  • electrode impdance range 200-900kOhms; check insulation by applying -3V to each electrode & looking for hydrogen bubbles.
  • soldering hardens platinum iridium alloy (huh).
  • (!!!) wires are stiffened for implantation by temporarily attaching them to a micropipette guide with sucrose which subsequently dissolves in the brain!
  • the smooth sucrose (40 grams in 50ml of water heated to 118C) coating requires about a week of desiccation to become hard enough for insertion into the brain without premature softening. Sucrose becomes clear like glass once fully desiccated.
  • the air above the craniotomy is sufficiently humid to dissolve the sucrose if left there for more than a few seconds.
  • used a miniature single-channel FET amplifier as a headstage - only one channel out of 6 could be recorded at once :( Thus their reults only apply to the best of the microwires implanted - not to all of them.
  • recorded onto a mac quadra (hahah) 20khz 12 bit
  • applying 160ua microstimulation pulses can restore low (200kohm) electrode impedance. Recording quality was generally improved for a few days following stimulation but then returned to an asymptotic level with the impedance at approximately 900kOhm.
  • electrodes only seemed to last 5 weeks, whence they declined to about 27% yeild - see figure 8.
  • good review of microelectrode recording up to that point (1997).

____References____

{736}
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ref: Liu-1999.09 tags: electrodes recording tissue response MEA histology date: 01-28-2013 00:24 gmt revision:7 [6] [5] [4] [3] [2] [1] [head]

PMID-10498377[0] Stability of the interface between neural tissue and chronically implanted intracortical microelectrodes.

  • implanted 7-shaft 35um iridium electrodes into the pericruciate gyrus of cats & measured the stability of recordings over several months.
  • electrodes were floating, under the dura; they note that connective tissue can force these floating arrays out of the brain, in further, or can encapsulate the electrodes.
    • electrodes activated by 'potentiodynamic cycling' to remove the insulation from the tip, I guess.
    • Insulation is epoxylite epoxy (5-10um thick) which is baked for curing and degassing at 100 and 170C each for 30 minutes.
    • more information on their fabrication in {1105}
  • Used the now-standard techniques for recording & analysis - amazing that this was all very new 10 years ago!
  • Measure stability not only on waveform shape (which will change as the position of the electrode relative to the neuron changes) but also neural tuning.
  • Lymphocytes were found to accumulate around the tips of the microstimulated sites.
  • Electrode sites that yielded recordings ('active') were all clean, with large neurons near the end, and with minimal connective tissue sheath (2-8 um; distance to nearby neurons was 30-50um).
    • Longest period for an active electrode was 242 days.
    • Electrode impedance was usually between 50 and 75 kOhm; there was no insulation failure.
  • Electrodes were stable even when the cat vigorously shook it's head in response to water placed on the head (!).
  • Electrodes were very unstable the first 2 weeks - 1 month ; rather stable thereafter.
    • Active electrodes tended to remain active ; inactive electrodes tended to remain inactive.

____References____

[0] Liu X, McCreery DB, Carter RR, Bullara LA, Yuen TG, Agnew WF, Stability of the interface between neural tissue and chronically implanted intracortical microelectrodes.IEEE Trans Rehabil Eng 7:3, 315-26 (1999 Sep)
[1] Bullara LA, McCreery DB, Yuen TG, Agnew WF, A microelectrode for delivery of defined charge densities.J Neurosci Methods 9:1, 15-21 (1983 Sep)

{746}
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ref: Sanders-2000.1 tags: polymer fiber immune reaction biocompatibility rats polycaprolactone recording electrodes histology MEA date: 01-28-2013 00:01 gmt revision:11 [10] [9] [8] [7] [6] [5] [head]

PMID-10906696[0] Tissue response to single-polymer fibers of varying diameters: evaluation of fibrous encapsulation and macrophage density.

  • Fibers smaller than 6μm show reduced immune response.
    • Fibers implanted in the subcutaneous dorsum (below the skin in the back of rats).
    • Polypropylene. (like rope).
    • Wish the result extended to small beads & small electrodes. 7μm is tiny, but possible with insulated Au wires.
      • Beads: try PMID-1913150 -- shows that the 600um - 50um beads ('microspheres') are well tolerated.
      • Also {750}.
  • Macrophage density in tissue with fiber diameters 2.1-5.9um comparable to that of unoperated contralateral control.

"

fiber diametercapsule thickness
2.1-5.90.6
6.5-10.611.7
11.1-15.820.3
16.7-26.725.5

____References____

[0] Sanders JE, Stiles CE, Hayes CL, Tissue response to single-polymer fibers of varying diameters: evaluation of fibrous encapsulation and macrophage density.J Biomed Mater Res 52:1, 231-7 (2000 Oct)

{897}
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ref: Harris-2011.08 tags: microelectrodes nanocomposite immune response glia recording MEA date: 01-27-2013 22:19 gmt revision:5 [4] [3] [2] [1] [0] [head]

PMID-21654037[0] In vivo deployment of mechanically adaptive nanocomposites for intracortical microelectrodes

  • J P Harris, A E Hess, S J Rowan, C Weder, C A Zorman, D J Tyler and J R Capadona Case Western University.
  • Simple idea: electrodes should be rigid enough to penetrate the brain, yet soft enough to not damage it once implanted.
  • Many studies have shown that shear stress around a microelectrode shaft causes neural die-off and glial response.
  • You can only record from neurons if they are < 100um from the electrode tip.
  • Nanocomposite material is inspired by sea cucumber skin.
    • Our materials exhibit this behaviour by mimicking the architecture and proposed switching mechanism at play in the sea cucumber dermis by utilizing a polymer NC consisting of a controllable structural scaffold of rigid cellulose nanofibres embedded within a soft polymeric matrix. When the nanofibres percolate, they interact with each other through hydrogen bonding and form a nanofibre network that becomes the load-bearing element, leading to a high overall stiffness of the NC. When combined with a polymer system which additionally undergoes a phase transition at physiologically relevant temperatures, a contrast of over two orders of magnitude for the tensile elastic modulus is exhibited.
  • Probes were 200um wide, 100um thick, and had a point sharpened to 45deg.
  • Buckle force testing was done on 53um thick, 125um wide probes sharpened to a 30deg point.
  • Penetration stress through the rat pia is 1.2e7 dynes/cm^2 for a Si probe 40um thick and 80um wide.
  • See also {1198}

____References____

[0] Harris JP, Hess AE, Rowan SJ, Weder C, Zorman CA, Tyler DJ, Capadona JR, In vivo deployment of mechanically adaptive nanocomposites for intracortical microelectrodes.J Neural Eng 8:4, 046010 (2011 Aug)

{1027}
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ref: Suner-2005.12 tags: MEA Utah reliability longevity SNR date: 01-25-2013 02:03 gmt revision:7 [6] [5] [4] [3] [2] [1] [head]

PMID-16425835[0] Reliability of signals from a chronically implanted, silicon-based electrode array

  • see {597}
  • Percutaneous connector used pressure-fitted pogo pins, as Gary was thinking of.
  • Utah array coated in parylene for this exp.
    • After implantation, array and cortex was covered in gore-tex (to prevent dura adhesion) -- they do not highlight this fact.
  • polyester insulated 25um gold wires as leads.
  • Reasonable SNR over 82, 172, 154 days.
  • One monkey had an array to 569 days -- 76 electrodes still provided good or fair waveforms.
  • ancilary (?) measure of tuning of the neurons. most neurons were not tuned.
  • SNR calculated as peak-peak of waveform divided by 2x standard deviation of signal.
  • A total of 36 implants in 16 other monkeys, which were not systematically evaluated for reliability here, provided successful recordings for up to 1264 days. Most of these studies ended because of headcap failure.
    • They no longer use dental acrylic -- only titanium bone screws.
  • 50-800K impedance
  • Improvement of the signal quality and increased yield, for which there was no clear trend in the three animals, may result from recovery produced by variations in the initial insertion injury.
  • The cortical capillary bed is densely packed, with spacing on the order of 40um in primate cortical tissue [27] ( vasculature ) -- they suppose that variance may be due to this.

____References____

[0] Suner S, Fellows MR, Vargas-Irwin C, Nakata GK, Donoghue JP, Reliability of signals from a chronically implanted, silicon-based electrode array in non-human primate primary motor cortex.IEEE Trans Neural Syst Rehabil Eng 13:4, 524-41 (2005 Dec)

{1205}
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ref: Rennaker-2005.03 tags: electrode recording longevity mechanical insertion Oklahoma MEA date: 01-25-2013 01:21 gmt revision:3 [2] [1] [0] [head]

PMID-15698656[0] A comparison of chronic multi-channel cortical implantation techniques: manual versus mechanical insertion.

  • Over 60% of the animals implanted with the mechanical insertion device had driven activity at week 6
    • whereas none of the animals with manually inserted arrays exhibited functional responses after 3 weeks.
      • Roughly identical responses immediately following surgery.
      • Could be that the manual inserter had horizontal movement / shear. (This is solveable with a stereotax).
      • Other research showed little difference in tissue response at 10um/s or 100um/s PMID-21896383[1]
  • Multi-wire electrodes.
  • Mechanical insertion device was capable of rapidly inserting the electrode without visible compression of the brain.
  • Response measured relative to auditory stimulus.
  • Their insertion device looks like a pen.

____References____

[0] Rennaker RL, Street S, Ruyle AM, Sloan AM, A comparison of chronic multi-channel cortical implantation techniques: manual versus mechanical insertion.J Neurosci Methods 142:2, 169-76 (2005 Mar 30)
[1] Welkenhuysen M, Andrei A, Ameye L, Eberle W, Nuttin B, Effect of insertion speed on tissue response and insertion mechanics of a chronically implanted silicon-based neural probe.IEEE Trans Biomed Eng 58:11, 3250-9 (2011 Nov)

{1033}
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ref: Seymour-2009.1 tags: Parylene MEA biocompatibility pin hole water saturation PPX date: 01-25-2013 01:19 gmt revision:2 [1] [0] [head]

PMID-19703712[0] The insulation performance of reactive parylene films in implantable electronic devices.

  • Describe the development and testing of a superior form of parylene: poly(p-xylylene) functionalized with reactive group X (PPX-X)
  • Heat-treated PPX-X device impedance was 800% greater at 10kHz and 70% greater at 1Hz relative to heated parylene-C controls after 60 days (in saline).
  • Better wet attachment to the metal.

____References____

[0] Seymour JP, Elkasabi YM, Chen HY, Lahann J, Kipke DR, The insulation performance of reactive parylene films in implantable electronic devices.Biomaterials 30:31, 6158-67 (2009 Oct)

{1026}
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ref: Thelin-2011.01 tags: histology MEA tether tissue response malmo lund date: 01-24-2013 22:17 gmt revision:5 [4] [3] [2] [1] [0] [head]

PMID-21298109[0] Implant size and fixation mode strongly influence tissue reactions in the CNS.

  • Overview: tethering and size both increase immune response, and causes continued GFAP activity.
    • An untethered 50um electrode exhibited very weak inflammatory response after 12 weeks.
      • Suggesting that a small electrode can move with the brain.
  • Tethering in their context means affixed rigidly to the bone.
    • Small-diameter, untethered implants cause the smallest tissue reactions.
    • Likely that this scales.
  • Stice et al 2007 {1111} -- GFAP expression was significantly smaller for 12 um diameter implants than 25um implants @ 4 weeks.
  • They used 50um and 200um stainless steel implants.
    • implants glued to micromanipulator using gelatine
  • 24 rats.
  • Much more GFAP and ED1 actviity in tethered implants; NEuN neural density about the same.
  • 50um implant had a higher NeuN + count.
  • Regarding implantation: not sure. Have to find a reference for stab wounds (where the inserter is retracted).

____References____

[0] Thelin J, Jörntell H, Psouni E, Garwicz M, Schouenborg J, Danielsen N, Linsmeier CE, Implant size and fixation mode strongly influence tissue reactions in the CNS.PLoS One 6:1, e16267 (2011 Jan 26)

{737}
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ref: Biran-2005.09 tags: microelectrode Michigan probe glia tissue response electrode immune histology MEA Biran date: 01-24-2013 20:49 gmt revision:5 [4] [3] [2] [1] [0] [head]

PMID-16045910[0] Neuronal cell loss accompanies the brain tissue response to chronically implanted silicon microelectrode arrays.

  • See also {1190} (wow, I'm redundant!)
  • Important point: ED1 up-regulation and neuronal loss were not observed in microelectrode stab controls, indicating that the phenotype did not result from the initial mechanical trauma of electrode implantation, but was associated with the foreign body response.
    • CD68 = ED1 is a marker for microglia and other macrophages. (wikipedia article is informative).
    • GFAP = glial fibrillary acidic protein, marker for astrocytes.
  • Recording failure is caused by chronic inflammation (mostly activated microglia) at the microelectrode brain tissue interface.
  • Only tested response 2 and 4 weeks after implantation. Makes sense for stab wound, but didn't the want to see a longer term response? Or do their electrodes just not last that long?
  • What did they coat the silicon probes in?
  • Used silastic to shock-mount their floating electrodes, but this apparently made no difference compared to conventional dental cement and bone screw mounting.
  • Suggest that chronic inflammatory response may be related to the absorption of fibrogen and complement to the surface of the device (device should not be porous?), the subsequent release of pro-inflammatory and cytotoxic cytokines by activated microphages, and the persistence of activated macrophages around materials which cannot be broken down.
    • Well then, how do you make the electrodes biochemically / biologically 'invisible'?
    • Persistently activated microglia are found around insoluble plaques in AD (plaques that cannot be / are not removed from the brain via proteolysis. Microglia form 'glitter cells' when they engulf undigestible stubstances). This has been termed 'frustrated phagocytosis', which results in increased secretion of proinflamatory cytokines that directly or indirectly cause neuronal death.
  • Significant reductions in neurofiliament reactivity was seen up to 230um from the microelectrode interface; this was not seen for stab wounds. Maximum recording distance is about 130um; 100um more reasonable in normal conditions.
  • Accumulating evidence from postmortem analysis of patients implanted with DBS electrodes reveals that chronic neuroinflamation is part of the response to such (duller, larger) implants as well. They have seen cell loss up to 1mm fromt the electrode surface here.

____References____

[0] Biran R, Martin DC, Tresco PA, Neuronal cell loss accompanies the brain tissue response to chronically implanted silicon microelectrode arrays.Exp Neurol 195:1, 115-26 (2005 Sep)

{1040}
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ref: Du-2011.01 tags: Harrison recording electrode MEA Blanche date: 01-04-2013 02:43 gmt revision:3 [2] [1] [0] [head]

PMID-22022568[0] Multiplexed, High Density Electrophysiology with Nanofabricated Neural Probes

  • The number of single-units possible to record doubles every 7 years [5].
  • Electrodes must be within 100um of soma to relaibly detect extracellular action potentials.
  • Existing Michigan arrays have trace features around >=1 um; here they use E-beam lithography to decrease the probe width dramatically.
    • Their wire widths are 290 nm. Still bigger than 40nm process (?)
  • Seem to use Reid Harrison's ASIC RHA22132 design.
  • noise of electrodes progressively decreased with consecutive gold electroplating cycles. Plating makes the electrodes rough, and decreases their impedance to around 1 M.
    • Electrode contacts are around 10 x 10 um square, 108 um^2 area.
  • Intrinsic noise of the amplifier 1.7 uV RMS.
  • 290 nm wire had an impedance of 9.2 k -- corresponding to 1.0 uV rms noise.
  • able to record from the same neuron from several adjacent electrodes. Spacing ~ 28 um.
  • Detail their process extensively -- 40% of probes survived the process with <= 5 defective channels. THey propose further optimization to the e-beam lithography. Probes took 7 hours to pattern on the lithography machine (!).

____References____

[0] Du J, Blanche TJ, Harrison RR, Lester HA, Masmanidis SC, Multiplexed, high density electrophysiology with nanofabricated neural probes.PLoS One 6:10, e26204 (2011)

{923}
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ref: Freire-2011.01 tags: Nicolelis BMI electrodes immune respones immunohistochemistry chronic arrays rats 2011 MEA histology date: 06-29-2012 01:20 gmt revision:5 [4] [3] [2] [1] [0] [head]

PMID-22096594[0] Comprehensive analysis of tissue preservation and recording quality from chronic multielectrode implants.

  • Says what might be expected: tungsten microelectrode arrays work, though the quality gradually declines over 6 months.
  • Histological markers correlated well with recording performance.
  • Shows persistent glial activation around electrode sites + cell body hypertropy.
    • Suggest that loss in recording quality may be due to glial encapsulation.
  • References
    • Szarowski et al 2003 {1028}
    • Ward et al 2009
  • Histology:
    • NADPH-d: nicotinamide adenine dinucleotide phosphate-diaphorase, via beta-NADP
    • CO: cytochrome oxidase, via diamnibenzidine DAB, cytochrome c and catalase.
      • both good for staining cortical layers; applied in a standard buffered solution and monitored to prevent overstaining.
  • Immunohistochemistry:
    • Activated microglia with ED-1 antibody.
    • Astrocytes labeled with glial fibrillary acid protein.
    • IEG with an antibody against EGR-1, 'a well-known marker of calcium dependent neuronal activity'
    • Neurofilament revealed using a monoclonal NF-M antibody.
    • Caspace-3 with the associated antibody
    • Details the steps for immunostaining -- wash, blocknig buffer, addition of the antibody in diluted blocking solution (skim milk) overnight, wash again, incubate in biotinylated secondary antibody, wash again, incubate in avidin-biotin-peroxidase solution.
    • Flourescent immunohistochemistry had biotynlation replaced with alexa Fluor 488-conjugated horse anti-mouse and Alexa Fluor 594-conjugated goat anti-rabbit overnight.

____References____

[0] Freire MA, Morya E, Faber J, Santos JR, Guimaraes JS, Lemos NA, Sameshima K, Pereira A, Ribeiro S, Nicolelis MA, Comprehensive analysis of tissue preservation and recording quality from chronic multielectrode implants.PLoS One 6:11, e27554 (2011)

{307}
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ref: Rousche-1998.07 tags: BMI Utah cat Normann recording electrode MEA histology date: 06-29-2012 01:12 gmt revision:9 [8] [7] [6] [5] [4] [3] [head]

PMID-10223510 Chronic recording capability of the Utah Intracortical Electrode Array in cat sensory cortex.

  • Focus on (surprisingly) chronic recording from the utah array: they want to demonstrate that it works.
  • Platinum coating.
  • insulated with 2-3um polymide.
  • 10 cats, 12 arrays: 2 in S1, 8 in auditory ctx, 2 V1.
  • 11 electrodes connected in each array.
  • After a 6-month implant period, 60% of implanted arrays could still record 'some type of activity'.
  • They were completely targeting neuroprostheses.
    • But acknowledge that 'the presence of fibrous encapsulation and chronic astrogliosis suggests that more research is necessary before the UIEA can be uses as a cornerstone of a neuroprosthetic device for human use.
      • And yet they went through with the human trials?
  • Electrode impedance gave no hint as to the ability of a given electrode to record neural units: many electrodes with average impedance could not record neural activity.
  • Impedances generally decreased , which is not unusual (Schmidt and Bak, 1976).
    • Likely that the polymide had become permeated with water vapor to and equilibrium point. (rather than pinhole leaks or water permeation).
  • Quiet amplifiers: 2uv pk-pk.
  • No significant trend in background activity was noted over the implant durations.
  • In nearly every cat, the dura above the electrode array adhered to the bone flap, and the electrode array adhered to the dura. Therefore, when the bone flap was removed, the UIEA was concurrently explanted from the cortex.
    • Similar to Hoogerwerf and Wise 1994 {1025}
    • The explanted UIEAs typically had become encapsulated, the encapsulation was the cause of the cortical depression.
    • Only 1 did not become encapsulated in dura.
    • This encapsulation explains the gradually varying recording properties -- the electrodes were moving out of the brain.
    • "The capsule which formed around the substrate of the UIEA was usually continuous with the dura, which was enmeshed directly to the overlying skull. The encapsulated array therefore had no freedom of movement with respect to the skull, and this may have caused local trauma which reduced the possibility of recording neural activity. This relative micromovement between the fixed array and the ‘floating’ cortical tissue may also be responsible for sustaining continued growth of the encapsulation as described above."
    • Have tried putting teflon on the top of the Utah array -- did this work?
  • Two UIEAs were not found near the cortical surface -- these two arrays were totally removed from the leptomeningeal space. although originally implanted into the cortex beneath the dura, at the time of sacrafice these arrays were found above the repaired dura, and the implanted cortex showed no evicence of cortical implant.
  • Some electrodes healthy; other showed chronic inflammation.
  • General and intense inflamation in the upper layers of cortex even on their best-performing array; no guarantee that this ctx was working properly, as it is heavily compressed with fibroblasts.
  • Regarding vascluature, see {1024}.
  • Say that the largest impediment is the formation of a capsule around the implant. (Do not mention issue of infection; I guess cats have strong immune systems as well?)
  • Rather good biological discussion and conclusion. worth a re-read. "We currently recommend that the UIEA be used for acute and short-term applications."
    • Not too many follow-ups re teflon or fixing the encapsulation problem: See {1026}
      • Indeed, {1027} doesn't even cite this! Too disastrous?

____References____

{1054}
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ref: Kawano-2010.03 tags: mEA recording VLS silicon original date: 01-15-2012 22:11 gmt revision:3 [2] [1] [0] [head]

PMID-20089393[0] Electrical interfacing between neurons and electronics via vertically integrated sub-4 microm-diameter silicon probe arrays fabricated by vapor-liquid-solid growth.

  • The probe arrays can be fabricated on a silicon (1 1 1) substrate by selective VLS growth using catalytic-gold (Au) dots and a disilane (Si2H6) gas source, allowing precise control of probe position, diameter and length, as well as on-chip interconnections/integrated circuits (ICs) ( [Wagner and Ellis, 1964], [Ishida et al., 1999] and [Kawano et al., 2002])
  • maximum length 120 um (or so)

____References____

[0] Kawano T, Harimoto T, Ishihara A, Takei K, Kawashima T, Usui S, Ishida M, Electrical interfacing between neurons and electronics via vertically integrated sub-4 microm-diameter silicon probe arrays fabricated by vapor-liquid-solid growth.Biosens Bioelectron 25:7, 1809-15 (2010 Mar 15)

{1025}
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ref: Hoogerwerf-1994.12 tags: Wise Michigan array MEA recording 3D date: 01-15-2012 07:12 gmt revision:4 [3] [2] [1] [0] [head]

IEEE-335862 (pdf) A three-dimensional microelectrode array for chronic neural recording.

  • see {995} for reasonable photos (they don't show up in the black and white IEEE scan).
  • 16-channel, 4 shanks.
  • 3D : 16 shanks, 64 channels, includes a 16:1 MNOS mux on the attached micromachined silicon platform.
  • Nickel plated lead stransfers (90 deg) see figure 6 electroplating current.
    • This was a point of difficulty, it seems.

____References____

Hoogerwerf, A.C. and Wise, K.D. A three-dimensional microelectrode array for chronic neural recording Biomedical Engineering, IEEE Transactions on 41 12 1136 -1146 (1994)

{740}
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ref: BeMent-1986.02 tags: Najafi Michigan probe recording silicon MEA date: 01-15-2012 06:59 gmt revision:6 [5] [4] [3] [2] [1] [0] [head]

PMID-3957372[0] Solid-state electrodes for multichannel multiplexed intracortical neuronal recording.

  • 1986 (!!) - but same basic technology for manufacture of these devices. Modern Michigan probes are much smaller, though - this paper uses 6um feature sizes. It seems like the rate-limiting step for a lot of this is marketization/selling it & getting the money for further R&D.
  • Mention closed-loop neuroprotheses ... 26 years ago. Why do we not have this yet? This is a really important question!
  • 12 channel on-chip analog processing, G=100, bandwidth 100-6kHz.
  • Mention that they think most of the current has to flow around other cells (glia), which makes it possible to record considerably further from the soma (ref [1],); see also PMID-14490040 which through modeling claims much smaller spread of current.
  • Electrode sites are highly capacitive, phase angle 80 deg.
  • 8 um interconnect leads.
  • Enhancement-mode LOCOS NMOS process.

____References____

[0] BeMent SL, Wise KD, Anderson DJ, Najafi K, Drake KL, Solid-state electrodes for multichannel multiplexed intracortical neuronal recording.IEEE Trans Biomed Eng 33:2, 230-41 (1986 Feb)

{308}
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ref: Kipke-2003.06 tags: Michigan rat Kipke recording electrode MEA date: 01-08-2012 03:34 gmt revision:5 [4] [3] [2] [1] [0] [head]

IEEE-1214707 (pdf) Silicon-substrate intracortical microelectrode arrays for long-term recording of neuronal spike activity in cerebral cortex.

  • 4 of the 6 implants (66%) remaining functional for more than 28 weeks (7 mo)
  • Recording sites separated by 100um; at this site separation, adjacent sites may sometimes record the same unit.
  • It is notable that in each case in this series was terminated due to reasons other than the microelectrode not recording unit activity. (SC LIn agrees, pc).
  • around 80% of sites recorded neural activity.

____References____

{997}
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ref: Najafi-1985.07 tags: Najafi original silicon michigan recording array 1985 MEA date: 01-06-2012 05:27 gmt revision:10 [9] [8] [7] [6] [5] [4] [head]

IEEE-1484848 (pdf) A high-yield IC-compatible multielectrode recording array.

  • Already talks about closed-loop control of a neuroprosthesis.
  • Started testing on-chip NMOS amplifiers.
  • tantalum and polysilicon conductors. some resistivity, but much less than the electrode interface.

____References____

Najafi, K. and Wise, K.D. and Mochizuki, T. A high-yield IC-compatible multichannel recording array Electron Devices, IEEE Transactions on 32 7 1206 - 1211 (1985)

{309}
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ref: Porada-2000.01 tags: electrodes recording oblique inverted MEA arrays Kruger date: 01-05-2012 23:07 gmt revision:3 [2] [1] [0] [head]

PMID-10776811[0] More than a year of recording with up to 64 microelectrodes

  • for more than a year action potentials of good quality were obtained from most electrodes!
  • used 60mm-long, 12.5um Ni-Cr-Al (Isaohm) wire, polyimide insulated, soldered to microconnectors. Tips purely ('primitively') cut after bonding them to a piece of photographic film substrate.
  • implanted in the rabbit and marmoset V1 cortex from afar.
  • with the 8 rabbits they used a magnetic release to prevent excessive force from removing the implant.
  • used small sections of thicker wire to individually label the electrodes for x-ray; thusly could reconstruct the electrode positions. electrodes in the white matter were silent mais or menos.
  • the autocorrelation functions of the neurons generally look good; some of them do not have a refractory period though.
  • in GFAP-stained sections a single electrode track appeared as a hole of about 28 um wide. The outer diameter of the wire insulation as 18um. electrode tracts were not visible in cresyl violet tracts. the neurones near the electrode tips appeared normal.
  • we recorded signals for up to 711 days, during which time the recording quality did not degrade. nice, nice!
  • they think that the large length of free wire, running about 5mm through the brain provides a sufficient degree of friction so that locally the tissue is prevented from moving relative to the electrodes. They did not need to use microstimulation to improve recording quality.

____References____

{1023}
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ref: Jones-1992.01 tags: Utah MEA original date: 01-05-2012 22:08 gmt revision:2 [1] [0] [head]

PMID-1510294[0] A Glass/silicon Composite Intracortical Electrode Array.

  • Describe fabrication of the Utah probe.
  • Needles 1.5mm long, 80um in diameter at the base, tapered.
  • 10 x 10 array on 400um spacing.
  • Impedance 10T ohm, capacitance 50fF
  • Old array used diamond dicing saw.
    • electrodes were isolated via p-n-p junctions, formed via thermomigration.
    • Too clever! These electrodes leaked & had poor yield.
  • New method: melt glass into shallow saw kerfs on the backside of a p-doped 1.83mm thick wafer, then remove much of the silicon from the top using the same saw. This produces columns of silicon held together at the base by glass.
    • Diamond dicing saw has a kerf of 50um. These things sound awesome.
    • Photopatterned aluminum electrode lands on the back.
    • Points are made by an acid etch.
    • Then plated in metal of some sort
    • Followed by polymide insulation (3-6um thick) (rather round from the SEM).
    • DC resistance of 10 to 20k.

____References____

[0] Jones KE, Campbell PK, Normann RA, A glass/silicon composite intracortical electrode array.Ann Biomed Eng 20:4, 423-37 (1992)

{1029}
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ref: McCarthy-2011.06 tags: titanium MEA Rao date: 01-05-2012 22:07 gmt revision:1 [0] [head]

PMID-21360044[0] Robust penetrating microelectrodes for neural interfaces realized by titanium micromachining.

  • Much stronger than silicon -- can make them thinner and smaller, less likely to fracture (?)
  • Think they may be pursuing the wrong goal here.

____References____

[0] McCarthy PT, Otto KJ, Rao MP, Robust penetrating microelectrodes for neural interfaces realized by titanium micromachining.Biomed Microdevices 13:3, 503-15 (2011 Jun)

{1031}
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ref: Kelly-2007.01 tags: MEA single electrode comparison CMU Utah date: 01-05-2012 22:07 gmt revision:1 [0] [head]

PMID-17215384[0] Comparison of recordings from microelectrode arrays and single electrodes in the visual cortex.

  • We found that the array yields good recordings on a large number of electrodes, with qualities comparable to those from single electrode recordings. On average, the recording quality is somewhat lower than that of single electrodes, but nonetheless is sufficient for assessing tuning properties such as the spatiotemporal receptive field and orientation tuning.

____References____

[0] Kelly RC, Smith MA, Samonds JM, Kohn A, Bonds AB, Movshon JA, Lee TS, Comparison of recordings from microelectrode arrays and single electrodes in the visual cortex.J Neurosci 27:2, 261-4 (2007 Jan 10)

{1032}
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ref: Dickey-2009.08 tags: Utah probe MEA stability date: 01-05-2012 22:07 gmt revision:1 [0] [head]

PMID-19535480[0] Single-unit stability using chronically implanted multielectrode arrays.

  • We found that 57% of the original units were stable through 7 days, 43% were stable through 10 days, and 39% were stable through 15 days.
  • Still not that good. Actual neurons / synapses last .. well, the lifetime of an individual.

____References____

[0] Dickey AS, Suminski A, Amit Y, Hatsopoulos NG, Single-unit stability using chronically implanted multielectrode arrays.J Neurophysiol 102:2, 1331-9 (2009 Aug)

{995}
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ref: QingBai and Wise-2001.08 tags: Bai Wise buffered MEA recording electrodes Michigan date: 01-05-2012 04:53 gmt revision:5 [4] [3] [2] [1] [0] [head]

IEEE-936367 (pdf) Single-unit neural recording with active microelectrode arrays

  • Design neural probes with on-chip unity-gain amplifiers. Proven to not degrade recordings (indeed, it should help!)
  • 200ohm output impedance
  • 11uV RMS noise, 100Hz-10kHz.
  • Multiplexer adds 8uV rms noise. noise from clock transitions 2ppm.
  • Also built amplifiers with 40db voltage gain (100x).

____References____

Qing Bai and Wise, K.D. Single-unit neural recording with active microelectrode arrays Biomedical Engineering, IEEE Transactions on 48 8 911 -920 (2001)

{996}
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ref: Najafi-1986.12 tags: Najafi implantable wired recording Michigan array multiplexing silicon boron MEA date: 01-05-2012 03:07 gmt revision:8 [7] [6] [5] [4] [3] [2] [head]

IEEE-1052646 (pdf) An implantable multielectrode array with on-chip signal processing

  • "The major reason for the slow progress in the understanding of neural circuits has been the lack of adequate instrumentation."
  • previous photolithographic: [4],[5]. Their first publication: [7].
  • Kensall Wise, not Stephen.
  • Single shank
  • 10 recording sites spaced at 100um
  • Amplifying 100x, b/w 15kHz., multiplexing.
  • width: 15um near tip, 160um at base.
  • 3 leads (!) power, ground, data.
  • 6um LOCOS enhancement and depletion NMOS technology -- not CMOS. (latter is prone to latch-up)
  • 5mW power.
  • boron dope silicon, etch back non doped portion with ethylenediamine-pyrocatechol (EDP) water solution.
  • must not have any substrate bias!

____References____

Najafi, K. and Wise, K.D. An implantable multielectrode array with on-chip signal processing Solid-State Circuits, IEEE Journal of 21 6 1035 - 1044 (1986)

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ref: Kuperstein-1981.03 tags: MEA Michigan probe MIT 1981 date: 01-05-2012 02:27 gmt revision:3 [2] [1] [0] [head]

IEEE-4121195 (pdf) A Practical 24 Channel Microelectrode for Neural Recording in Vivo

  • Molybdenum substrate (??).
  • progenitor to the Michigan probe?

____References____

Kuperstein, Michael and Whittington, Douglas A. A Practical 24 Channel Microelectrode for Neural Recording in Vivo Biomedical Engineering, IEEE Transactions on BME-28 3 288 -293 (1981)

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ref: Schmidt-1980.01 tags: BMI 1980 SUA M1 prosthetics Schmidt MEA date: 01-04-2012 22:59 gmt revision:14 [13] [12] [11] [10] [9] [8] [head]

PMID-6794389[0] Single neuron recording from motor cortex as a possible source of signals for control of external devices

  • also [1]
  • I guess this was the first published article claiming that motorneurons could be used to drive a prosthesis, and first clear attempt at long-term array recording (?)
  • recorded via arrays for up to 37 months!
    • only 2 of the 11 eelctrodes were recording at the time of sacrifice.
  • trained the monkey to perform an 8 target tracking task
    • with cortical neurons: 2.45 bits/second
    • with wrist flexion/extension: 4.48 bits/second
  • electrodes: {946} A new chronic recording intracortical microelectrode (1976!)
    • 25um iridium wires electropolished to a 1um tip; 1.5mm long.
    • electrodes float on the cortex; signals transmitted through 25um gold wire, which is in turn connected to a head-mounted connector.
    • iridium and gold are insulated with vapor-deposited parylene-C
    • electrode tips are exposed with a HV arc. (does this dull them? from the electromicrograph, it seems that it just makes them rougher.)
    • arrays of 12.
    • 1M impedance (average)
  • interesting: neural activity was recorded from at least 8 different neurons with this electrode during the course of the implant, indicating that it was migrating through cortical tissue.
    • the average recording time from the same electrode was 8 days; max 23 days.
  • second implant was more successful: maximium time recording from the same neuron was 108 days.
  • failure is associated with cracks in the parylene insulation (which apparently occurred on the grain boundaries of the iridium). "still only marginally reliable" (and still.. and still..)
  • they have operantly trained cortical units in another, earlier study.
  • have, effectively, 8 levels of activity, with feedback monkey has to match the proscribed firing rate.
  • > 50% rewarded trials = success for them; 26/28 of the neurons tested were eventually conditioned successfully.
  • looks like the monkey can track the target firing rate rather accurately. "the output of cortical cells can provide information output rates moderately less precise than the intact motor system. "
  • Monkey can also activated sequences of neurons: A, then AB, then B.
  • people have also tried conditioning individual EMG units; it is sometimes possible to control 2 different motor units in the same muscle independently, but in general only a single channel of information can be obtained from one muscle, and gross EMGs are fine for this.
    • Thus surface EMG is preferred.
    • you can get ~ 2.73 bits/sec with gross EMG on a human; 2.99 bits/sec (max) with a monkey.
  • they remind us, of course, that an enormous amount of work remains to be done.

____References____

{1019}
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ref: Chorover-1972.1 tags: sweet electrode MEA Chorover date: 01-04-2012 03:00 gmt revision:2 [1] [0] [head]

PMID-4670862[0] A sweet new multiple electrode for chronic single unit recording in moving animals.

  • 7 or more 25um individually teflon coated Pt-Ir wires
  • Supported by 26ga hypodermic tubing.
  • coated in melted dextrose (no water, keep stirring it) via dipping.
  • connection via colloidal silver epoxy. we use that.
  • Units recorded within 48 hours. "Electrodes cmoe to exhibit ha high degree of shock-resistance and neurtral bouyancy with respect to immediately-adjacent brain tissue."
  • Durable to 2-3 months of 51 individual electrodes in 8 rats.
  • 1kHz impedance 500k.

____References____

[0] Chorover SL, DeLuca AM, A sweet new multiple electrode for chronic single unit recording in moving animals.Physiol Behav 9:4, 671-4 (1972 Oct)

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ref: Thomas-1972.09 tags: MEA electrodes cell culture platinum black date: 01-04-2012 02:40 gmt revision:6 [5] [4] [3] [2] [1] [0] [head]

PMID-4672477[0] A miniature microelectrode array to monitor the bioelectric activity of cultured cells

  • Designed for heart cells.
  • 30-element muilt into the cluture chambers.
  • Utilizes PCB lithography technology. Indeed, the insulation is photoresist / 'photopolymer'.
  • platinum black

____References____

[0] Thomas CA Jr, Springer PA, Loeb GE, Berwald-Netter Y, Okun LM, A miniature microelectrode array to monitor the bioelectric activity of cultured cells.Exp Cell Res 74:1, 61-6 (1972 Sep)

{1016}
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ref: Lilly-1958 tags: Lilly MEA original neural tuning date: 01-04-2012 02:15 gmt revision:4 [3] [2] [1] [0] [head]

bibtex: Lilly-1958 Correlations between Neurophysiological Activity in the Cortex and Short-Term Behavior in the Monkey

  • 610 channels in 'Susie'! Unable to record from all of them for lack of recording technology.
  • references the rest of his work.
  • Was able to elicit pretty dramatic and fascinating stimulation responses:
    • 'shrink' as if warding off a blow to the contralateral side of the head;
    • at an adjacent electrode we found a pattern called 'goose', this pattern involved the whole body, and the reaction looks as if the monkey had been forcefully, mechanically stimulated par anum.
    • both were accompanied by high arousal.
  • Suggest that behavioral frequency-of-use corresponds rounghly to cortical rank-area order.
  • Note that the wave velocity (as imaged by his bavatron) in cortex can vary dramatically, from 1 m/sec to 0.1 m/sec.
    • With practice, one can see the boundaries between the 'arm' and 'leg' regions quite easily.
  • Stated our problem quite concisely: "One of the large difficulties in correlating structure, behavior, and CNS activity is the spatial problem of getting enough electrodes, and small enough electrodes, \emph{in} there with minimal injury. (This is why he was usnig pial electrodes). Still another problem is getting enough samples from each electrode per unit time, over a long enough time, to see what goes on during conditioning or learning [...] s for the problem of the investigator's absorbing the data -- if he has adequate recording techniques, he has a lot of time to work on a very short recorded part of a given monkey's life."
  • no figures :-(
  • Lilly could publish. a b -- though he appears to have ADHD (perhaps from the LSD)
    • also see his homepage -- He died in 2001, but it's still up.
  • images/1016_1.pdf

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ref: Lilly-1950 tags: Lilly original MEA glass pipette date: 01-04-2012 01:52 gmt revision:4 [3] [2] [1] [0] [head]

bibtex:Lilly-1950 A Method of Recording the Moving Electrical Potential Gradients in the Brain. The 25-Channel Bavatron and Electro-Iconograms.

  • images/1017_2.pdf
  • Every cell in the cortex is within 25 um of a capillary (!). Really?
  • You can already see him wanting to record from whales / dolphins.
  • Used electrode arrays and photocathode tubes to record from cat.
  • 8x8mm array, 2mm spacing, 100um tip opening in the glass pipettes.
    • Pipettes could slide up & down to rest gently on the pia.
    • Were filled via capilary action
    • Both acute and chronic recording.
  • 1mm spacing of electrodes would still record on the order of 5,000 neurons; good thing there is exponential space dependence.
    • Resistance 50k, low so that thermal noise has little effect.
  • recorded 3,500 feet of film (!!); 1,200 feet of film accumulates in two minutes; this takes 48 minutes to see once.
  • Results in preparation ... were they ever published? where? Must have been nearly impossible to analyze without a computer!

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ref: Nicolelis-2003.09 tags: nicolelis recording electrode monkeys MEA date: 01-04-2012 01:23 gmt revision:3 [2] [1] [0] [head]

PMID-12960378 Chronic, multisite, multielectrode recordings in macaque monkeys.

  • max 412 neurons, snr 5
  • up to 18 months, with precipitous decline
  • Miguel is the first author. well, that only makes sense.

____References____

{1011}
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ref: Goldstein-1973.07 tags: Salcman microelectrodes bucking analysis stiffness youngs modulus mechanical MEA date: 01-04-2012 01:22 gmt revision:4 [3] [2] [1] [0] [head]

IEEE-4120642 (pdf) Mechanical Factors in the Design of Chronic Recording Intracortical Microelectrodes

____References____

Goldstein, Seth R. and Salcman, Michael Mechanical Factors in the Design of Chronic Recording Intracortical Microelectrodes Biomedical Engineering, IEEE Transactions on BME-20 4 260 -269 (1973)

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ref: MolinaLuna-2007.03 tags: ICMS microstimulation cortical thin-film electrodes histology MEA date: 01-03-2012 22:54 gmt revision:2 [1] [0] [head]

PMID-17178423[0] Cortical stimulation mapping using epidurally implanted thin-film microelectrode arrays.

  • they claim that thin-film electrodes are better than microelectrode arrays, as they show less evidence of cortical damage.
    • thin-film electrodes show higher reproducability
    • more accurate spatial arrangement.
  • epidural stimulation (they were implanted between the dura and skull)

____References____

[0] Molina-Luna K, Buitrago MM, Hertler B, Schubring M, Haiss F, Nisch W, Schulz JB, Luft AR, Cortical stimulation mapping using epidurally implanted thin-film microelectrode arrays.J Neurosci Methods 161:1, 118-25 (2007 Mar 30)

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ref: Najafi-1990.05 tags: Najafi Michigan probe silicon strength electrodes recording MEA date: 01-03-2012 22:45 gmt revision:5 [4] [3] [2] [1] [0] [head]

PMID-2345003[0] Strength characterization of silicon microprobes in neurophysiological tissues.

  • These active (with amplification/buffering circuitry) electrodes were around since 1990! It's been a while, and at least the devices are commercially available now.
  • Show that thin-film silicon is remarkably flexible and tough - about six times as strong as bulk silicon.
  • Have developed a silicon probe with an integrated phosphorous-doped polysilicon strain guague - nice.

____References____

[0] Najafi K, Hetke JF, Strength characterization of silicon microprobes in neurophysiological tissues.IEEE Trans Biomed Eng 37:5, 474-81 (1990 May)

{1012}
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ref: Wise-1970.07 tags: Wise MEA silicon gold lithography date: 01-03-2012 19:05 gmt revision:3 [2] [1] [0] [head]

IEEE-4502738 (pdf) An Integrated-Circuit Approach to Extracellular Microelectrodes

  • Used lithography techniques & to make SiO2 & Au electrodes.
  • 2um tips.
    • Back then, small tips were deemed good; nowadays, we want larger, lower-impedance tips (fad?)
  • Most previous work is glass insulated metal electrodes [1][2]
    • C. Guld, a glass-covered platinum microelectrode. {1014}
  • Probes cannot exceed more than 50um from the edge of the chip carrier without cracking, which limits how close one may get to a given cell.

____References____

Wise, Kensall D. and Angell, James B. and Starr, Arnold An Integrated-Circuit Approach to Extracellular Microelectrodes Biomedical Engineering, IEEE Transactions on BME-17 3 238 -247 (1970)

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ref: Nicolelis-2011 tags: Nicolelis beyond boundaries MEA date: 01-03-2012 18:06 gmt revision:5 [4] [3] [2] [1] [0] [head]

Beyond Boundaries: The New Neuroscience of Connecting Brains with Machines - and How It Will Change Our Lives

  • Lashley removed parts of the brain after training animals (vivisectionist) "In fact, if just one-sixtieth of the primary visual cortex remained, the animal would retain a visual-motor habit it had learned."
  • Adrian 1946 ... Nobel prize 1932 .. Volta 1783.
  • Thomas Young, of Young's double slit experiment.
  • Franz Gall, Phrenologist.
  • Stanley Finger __Origins of Neuroscience__
  • Broca 1861
  • Cajal's discovery of neurons.
  • Cytoarchitectonics was launched into prime time, at least in part, by the Russian histologist Vladimir Betz’s discovery in 1874 that the motor cortex, the cortical region that Hitzig and Fritsch had tagged as the source of body movements, contained a peculiar horizontal layer packed with large pyramid-shaped neurons.
  • The German neurologist Korbinian Brodmann introduced, in a series of papers published between 1903 and 1914, a comprehensive cytoarchitectonic classification, based on Nissl staining, suggesting that the mammalian cortex comprised fifty-two cortical fields
  • Penfield was a student of Sherrington. Hebb collaborated with Penfield to create the Homunculus.
  • Phantom limb pain ... Melzack in the 1980s.
  • Rubber hand illusion. Saw a bit of that today with prism goggles.
  • Recording: Eccles, Mountcastle, who established the idea of a 'cortical column'.
  • John Cunningham Lilly and his friend Edward Evarts devised the first sensory deprivation chamber.
    • Lilly was of the first to record from non-anesthetized animals.
    • 25 channels! Filmed the responses as amplified on glow-tubes!
    • Lilly also came up with a charge-balanced wave for ICMS.
    • Lilly managed to implant 610 electrodes -- the electronics was not up to the age, though. (now it is!)
    • In contrast Evarts focused on one neuron at a time, well isolated.
      • Quote: In some cases, neurophysiological experiments seem to have morphed into tautological exercises, in which authors report, usually with great excitement, that after many months of intense behavioral training and painstaking analysis of neuron firing patterns, they were capable of identifying a few neurons whose activity correlates with some of the task’s main attributes.
  • Regarding the inception of the MEA: Because of the larger exposed area of the microwire tips, he postulated that the inflammatory reaction would not be sufficient to block a tip’s entire surface. Instead, the inflammatory deposits would actually improve the quality of the microwire’s recordings over the first two weeks or so, morphing it from an electrode with low to one with high resistance.
    • Hmm. Low resistance is good.
  • Fairly in-depth review of Fetz and Finnochio's work with EMG recruitment & how M1 & EMG could be dissociated.
  • Tool incorporation & Iriki / Hemi-neglect and strokes.
  • The Quark and the Jaguar by Murray Gell-Mann
  • Delgado is still alive; Miguel got permission from him to use the images of the bull etc.
    • Talks about manipulating social hierarchies. This got him notoriety, and not all of the good sort: wireheading.

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ref: Tian-2010.08 tags: nanowire nanoprobe silicon FET doping cis trans extracellular intracellular recording neuro MEA date: 01-03-2012 16:35 gmt revision:4 [3] [2] [1] [0] [head]

PMID-20705858[0] Three-Dimensional, Flexible Nanoscale Field-Effect Transistors as Localized Bioprobes

  • Made a silicon nanowire with 60 deg. kinks via trans/cis manipulation.
  • Doped one part of the N nanowire P to make a 200nm long FET whose gate is simply the surface of the nanowire (I think, have to check the refs)
  • Attached the nanoprobe / nanowire to flexible PMMA / SM-8 support which, due to interfacial stress, rose off the substrate (clever!)
  • Coated tip with phospholipid layers -> better cell attachment / penetration.
    • Possible to have the cell pull the nanoprobe in via endocytic pathways.
  • Were able to record intracellular and extracellular AP from rabbit cardiocytes. (!!!)

____References____

[0] Tian B, Cohen-Karni T, Qing Q, Duan X, Xie P, Lieber CM, Three-dimensional, flexible nanoscale field-effect transistors as localized bioprobes.Science 329:5993, 830-4 (2010 Aug 13)

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ref: Pearce-2004.01 tags: neural recording microfluidics in-vitro MEA date: 01-03-2012 06:53 gmt revision:4 [3] [2] [1] [0] [head]

PMID-17271187[0] Dynamic control of extracellular environment in in vitro neural recording systems.

  • they show how to create microfluidic channels on top of in-vitro microfluidic arrays.
  • used dorsal root ganglion cells.
  • key aspect:
    • make a thin cavity/space between two polycarbonate panes.
    • fill the cavity with liquid-phase isobornyl acrylate
    • cover the panes with a high-resolution mask
    • upon exposure to UV light the isobornyl polymerizes.
    • did this on top of a MEA-60
  • looks like they can very accurately deliver pulses and streams of fluid.

____References____

[0] Pearce T, Oakes S, Pope R, Williams J, Dynamic control of extracellular environment in in vitro neural recording systems.Conf Proc IEEE Eng Med Biol Soc 6no Issue 4045-8 (2004)

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ref: Blum-2004.01 tags: microstimulator MEA Georgia Blum integrated circuit date: 01-03-2012 06:53 gmt revision:3 [2] [1] [0] [head]

PMID-17271195[0] Models of stimulation artifacts applied to integrated circuit design.

  • for MEAs.
  • Idea: develop a model of the stimulation artifact so they can optimize removal in SPICE.
  • reference documents that say that biphasic stimulation + active artifact suppression (by discharging the electrodes after stimulation, [1]) are acknowledged means of reducing stimulus artifact.
  • artifact appears to be 1ms saturating, 6ms non-saturating pulse.
  • a little light on details.

____References____

[0] Blum R, Ross J, Das S, Brown E, Deweerth S, Models of stimulation artifacts applied to integrated circuit design.Conf Proc IEEE Eng Med Biol Soc 6no Issue 4075-8 (2004)
[1] Jimbo Y, Kasai N, Torimitsu K, Tateno T, Robinson HP, A system for MEA-based multisite stimulation.IEEE Trans Biomed Eng 50:2, 241-8 (2003 Feb)

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ref: notes-0 tags: k-means clustering neurophysiology sorting date: 01-03-2012 06:51 gmt revision:1 [0] [head]

k-means is easy!

% i want to do the k-means alg. 
v = [x y]; 
nc = 7;
dim = cols(v); 
n = rows(v); 
cent = rand(nc,dim); 
d = zeros(n, nc); 
for k = (1:500)
	for s = 1:nc
		d(:,s) = sqrt(sum((v - rvecrep(cent(s, :), n)).^2,2));
	end
	% select the smallest
	[nada, g] = min(d'); 
	g = g';
	for s = 1:nc
		if(numel(find(g==s)) > 0)
			cent(s, :) = mean(v(g==s, :));
		end
	end
end

real data from clementine:

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ref: Lebedev-2006.09 tags: misha lebedev nicolelis BMI past present future electrodes review MEA date: 01-03-2012 03:26 gmt revision:2 [1] [0] [head]

PMID-16859758 Brain-machine interfaces: past, present and future.

  • Describes the state of the art & what needs to be done. Namely, better recording quality.
  • state that current EEG BMIs are limited to 5-25 bits/min (typo!!) [2,11]
    • [2] Wolpaw "Brain-computer interfaces for communication and control" 2002.
    • [11] Birbaumer "Brain-computer-interface research: coming of age" 2006.
  • set of references on biofeedback control of EEG in research animals.
  • EEG BCIs are either biofeedback based or classifier (P300, synchronous decoder ) based.
  • First invasive BMIs Fetz [40-45], Schmidt [46]; progress has been limited by technology. Must have been quite challenging for him to do the research!
    • [40] Fetz "Operant Conditioning of cortical unit activity" 1969
    • [41] Fetz "Are movement parameters recognizably coded in activity of single neurons?" 1992
    • [42] Fetz and Baker "Operantly conditioned patterns on precentral unit activity and correlated responses in adjacent cells and contralateral muscles." 1973
    • [43] Fetz and Finocchio "Operant Conditioning of specific patterns of neural and muscular activity" 1971
    • [44] Fetz and Finocchio "Operant conditioning of isolated activity in specific muscles and precentral cells" 1972
    • [45] Fetz and Finocchio 1975 "Correlations between activity of motor cortex cells and arm muscles during operantly conditioned response patterns." 1975
    • [46] Schmidt "single neuron recording from motor cortex as a possible source of signals for control of external devices." 1980
  • microelectrode arrays solved one of the problems.
  • talk about how more neurons are needed.
  • Principles of BMIs: Evarts [66-68], neuronal modulations are highly variable [69-72].
    • [66] Evarts, E.V. (1966) Pyramidal tract activity associated with a conditioned hand movement in the monkey.
    • [67] Evarts, E.V. (1968) Relation of pyramidal tract activity to force exerted during voluntary movement.
    • [68] Evarts, E.V. (1968) A technique for recording activity of subcortical neurons in moving animals.
    • "THus, as much as neighboring neurons might display highly disinct firing modulation patterns during the execution of a particular movement, single-neuron firing can vary substantially from one trial to the next, despite the fact that the overt movements remain virtually identical. :
    • "averaging across large populations of neurons significantly reduces the variability of signals derived from single neurons [54, 69].
    • Should i mention this in thesis?
  • Better way to assimilate the BMI into the body is to have proprioceptive feedback.
  • suggest the same standard things to be improved, excluding electronics. :
    • electrodes / recording
    • decoding
    • incorporating plasticity
    • better prosthetics.
  • "multi-unit signals can also be efficiently used in BMI control [57] {318}.
  • Some groups have strongly claimed that recordings from a small number of neurons can be sufficient for good performance in a BMI. [55,56,63]
    • This is not Miguel's approach: more neurons confers accuracy [54{317},57,70] and reliability [69].
      • [70] Wessberg, J. and Nicolelis, M.A. (2004) Optimizing a linear algorithm for real-time robotic control using chronic cortical ensemble recordings in monkeys. J. Cogn. Neurosci. 16, 1022–1035
  • Still need new microelectrodes; electrodes become encapsulated by fibrous tissue and cells die in the vicinity of electrodes [77] {781}.
    • suggest anti-inflammatory coating, though the jury is out.
  • Initial wireless telemetry systems: [93-99]. [93]{315}
    • [94] Knutti, J.W. et al. (1979) An integrated circuit approach to totally implantable telemetry systems. Biotelem. Patient Monit. 6, 95–106
    • [97] Chien, C.N. and Jaw, F.S. (2005) Miniature telemetry system for the recording of action and field potentials. J. Neurosci. Methods 147
    • [98] {930}
    • [99] Morizio Morizio, J. et al. (2005) Fifteen-channel wireless headstage system for single-unit rat recordings.
    • [100] (of broader interest) Moxon, K.A. et al. (2004) Ceramic-based multisite electrode arrays for chronic single-neuron recording. IEEE Trans. Biomed. Eng. 51, 647–656
  • nanotechnology probes that access the brain through the vasular system [101].
  • although a good number of linear and nonlinear algorithms have been proposed and tested [1,54,56,57,70,110-116], Wiener filters have proved sufficient [54,55,57,58,65,117].
  • almost 140 years ago Head and Holmes suggested that the body schema -- that is, the internal brain representation of one's body -- could extend itself to include a wielded tool.

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ref: WISE-2004.01 tags: wireless electrodes silicon Michigan Kipke Najafi recording MEA date: 01-03-2012 03:23 gmt revision:12 [11] [10] [9] [8] [7] [6] [head]

IEEE-01258173 (pdf) Wireless implantable microsystems: high-density electronic interfaces to the nervous system - January 2004.

  • very impressive!
  • based on the old / well established beam-lead technology (see the image of the paper at the bottom of that page).
    • required 20 years of development to create an etching process with sufficient yield, though. Microprobes have been in development since 1966.
    • Silicon is slowly attacked by saline; however, the use of a boron etch-stop to define the substrate virtually eliminates such erosion.
    • Silicon dioxide is known to slowly hydrate in water, but this can be mitigated by CVD of silicon nitride / silicon oxide stacks. Polysilicon can be used too, since it forms a tight bond with silicon oxide, keeping water out.
      • Why don't they just seal it with a known impermeable plastic/epoxy/whatever? (They do, later) Utah probe is sealed in parylene.
    • Shunt capacitance is negligible compared to site capacitance; heavy substrate doping minimizes electrical or optically induced noise & virtually eliminates crosstalk.
    • (Of course) Silicon allows amplifiers and circuitry to be formed at/near the electrode, eliminating the need for (some) interconnects.
    • Silicon ribbon connectors cannot be made much longer than a few centimeters. 4um thick silicon cables are 100x more flexible than a 25um gold wire (!!) - but that is out-of-plane; they are relatively weak for in-plane stress.
  • Gold has a maximum charge delivery of 20uC/cm^2 ; platinum, 75 uC/cm^2 ; iridium oxide, 3000 uC/cm^2.
  • Glass can be hermetically bonded to silicon if both flat clean surfaces are put in opposition with a high voltage (1500V) placed across the interface at an elevated temperature (400C). These packages have been shown to be stable and inert in guinea pigs.
    • Silicon nitride, thin metal films, and metal films over polymers are all attractive coatings for probes (with no mention of biocompatibility); they last decades in salt water, and eventually succumb to pinholes.
  • Silicon probes outperform microwire arrays by a factor of (up to) 50 in terms of volume of tissue displaced / recording site. Michigan probes are typically 15um thick x 60um in cross section.
  • they tend to use many more recording sites than recording channels, hence, have a low expected yield. e.g. they have a 1024 site electrode (see the cool figures!), and can record from the best 128 of those. good idea, reasonable strategy, I guess.
    • they demonstrate that it is not too hard to remove the artifact of multiplexing on their systems - the multiplexing noise is below electrode noise.
  • talk about spongifying their iridium electrodes using current pulses in a PBS solution to (apparently) lower electrode impedance.
  • talk about drug delivery too
  • describe the exact manufacturing procedures that the Michigan arrays are created, including the critical back-etch (which i don't exactly understand).
  • describe the circuits used to amplify low-level neural signals.
  • Their charge-redistribution ADC is okay - 250ksps, 9b resolution, 1.4mW from a 3v source. Commercial ADCS are better - AD7467 is 0.6mw, 200ksps, 10bits. (though it scales up to 1.3mW @ 3V, 200ksps ; 0.36mW @1.8V - so the devices are comparable.)
  • some of the (very tiny) electrodes have 'holes' (!)
  • also have wireless microstimulators.
  • demonstrate long-term recording: 383days post implant in a rat & there are still many cells (though the figure is not that great, it is easy to understand) (this might be an exemplar)
  • associated website?
  • (quote:) "For ranges of a few centimeters, the high attenuation of RF signals in biological tissue dictates carrier frequencies below 10Mhz." Their solution is to use FSK with octave jumps in freqency & modulation rates up to 60% that of the carrier frequency.

____References____

WISE, K.D. and ANDERSON, D.J. and HETKE, J.F. and KIPKE, D.R. and NAJAFI, K. Wireless implantable microsystems: high-density electronic interfaces to the nervous system Proceedings of the IEEE 92 1 76 - 97 (2004)

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ref: Csicsvari-2003.08 tags: recording michigan silicon electrodes Buzsaki MEA date: 01-03-2012 03:23 gmt revision:4 [3] [2] [1] [0] [head]

PMID-12904510[0] Csicsvari 2003 Massively parallel recording of unit and local field potentials with silicon-based electrodes

  • What's so massive? 64 or 96 channel Michigan probes.
  • Motivation: recording local connections and interactions requires precise knoledge of the location of your recording sites.
  • Some classic refs on cortical building blocks.
  • Optical recording: Mao et al 2001 PMID-11738033.
  • Wired recording:, Chicurel 2001; Deadwyler and Hampson 1995 PMID-7481817; Evarts 1968; {994}
  • Tetrodes: Drake 1988, Gray 1995, McNaughton et al 1983; Recce and O'Keefe 1989.
  • on-chip active circuitry (simple voltage feedback op-amp - without reference electrodes!) reduces microphone artifact. 6mm 'antenna'.
    • refs: Bai and Wise 2001 {995}; Olsson et al. 2002
    • also Najafi and Wise 1986 {996}; Wise and Najafi 1991 .
  • Stored wideband data; sorted via KlustaKwik.
  • Total recording area 1.6mm deep by 1.8mm wide. Shanks separated by 300um ; recordings sites separated by 100um; shanks 12um thick.
    • Made via double-sided deep reactive reactive ion etching (DRIE).
  • stimulated the entorhinal cortex & recorded in the hippocampus; used the precise spatial layout of the micromachined silicon electrodes to map out the evoked potentials.
  • figure 3 shows that they can record the 'same' neuron from multiple 100um-spaced sites on a given shank. Some of this is due to the physically large extent of the hippocampal cells which they recorded; spike propagate both down the axon and back into the soma, and by using Current Source Density maps, they could estimate some of spatio-temporal characterisics of the AP.
    • CSD is the second spatial derivtive of the local field potentials.
    • Could measure forward and back-propagation of APs to the dendrites (!)
  • quote: in contrast to wire tetrodes with blunt cute ends, it was possible to record from the same cell layer numerous times after moving the probe up and subsequently back to the previous recording location.
    • size of the electrode shanks: 62um wide x 12um thick at top of recording site of 12 site shank; 82um wide at top of 16 site shank.
    • Top 4 recording sites' recording quality deteriorated with multiple penetrations.
  • good place-cell map; cells were discriminated based on a PCA across both time and electrode.

____References____

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ref: Otto-2006.02 tags: electrophysiology recording rejuvenation stimulation MEA date: 01-03-2012 03:21 gmt revision:3 [2] [1] [0] [head]

PMID-16485763[0] Voltage pulses change neural interface properties and improve unit recordings with chronically implanted microelectrodes.

  • stimulation protocol: 1.5 volts, cortical electrode positive, 4 seconds, DC, current measured.
  • results: 10% mean improvement in SNR (not that great, oh well)
    • however, some effects were really profound: complete rejuvenation of the recordings!
  • result: 67% lower impedance.

____References____

[0] Otto KJ, Johnson MD, Kipke DR, Voltage pulses change neural interface properties and improve unit recordings with chronically implanted microelectrodes.IEEE Trans Biomed Eng 53:2, 333-40 (2006 Feb)

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ref: Williams-1999.12 tags: recording microwire guinea kipke MEA Michigan date: 01-03-2012 03:18 gmt revision:2 [1] [0] [head]

PMID-10592339[0] Long term neural recording characteristics of wire microelectrode arrays implanted in cerebral cortex

  • details the williams microwire array assembly protocol - basically the same as what gary does here in the nicolelis lab, only written up nicely and for guinea pigs not rhesus macaques.
  • references miguel's book on multielectrode recordings

____References____

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ref: Verloop-1984.08 tags: recording electrode arrays MEA epoxy teflon simple mold slice cultures date: 01-03-2012 00:57 gmt revision:2 [1] [0] [head]

PMID-6492861[0] A simple method for the construction of electrode arrays.

  • It is simple!
  • of note: "Therefore arrays of equidistant electrodes have been developed for superficial and depth recording. During the last decade the construction of many of these multiple electrodes for in vivo and in vitro measurements is based o n thin film techniques (Wise a n d Angell, 1975; Pickard, 1979; Pochay et al., 1979; Prohaska et al., 1979; Kuperstein and Whittington, 1981).
    • Have to go back and check these thin-film attempts.
  • See also: PMID-7248818[1] A flexible high density multi-channel electrode array for long-term chronic implantation. (surface recording).

____References____

[0] Verloop AJ, Holsheimer J, A simple method for the construction of electrode arrays.J Neurosci Methods 11:3, 173-8 (1984 Aug)
[1] Weissman AD, Schwartz EL, A flexible high density multi-channel electrode array for long-term chronic implantation.Brain Res Bull 6:6, 543-6 (1981 Jun)

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ref: Nicolelis-2002.1 tags: Nicolelis MEA electrodes recording date: 01-03-2012 00:57 gmt revision:1 [0] [head]

PMID-12367642[0] Multielectrode recordings: the next steps.

  • Ensemble recordings have actually been around for a long time -- Schmidt, at least.
    • 100s of electrodes, however, have not.
  • Predicted the death of single unit recordings and the emergence of 1000s of channels with indefinite longevity.
  • Also talk about gene arrays & antisense RNA & cre/loxP. Oldish.

____References____

[0] Nicolelis MA, Ribeiro S, Multielectrode recordings: the next steps.Curr Opin Neurobiol 12:5, 602-6 (2002 Oct)

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ref: Brown-2008.03 tags: microstimulation recording artifact supression MEA ICMS date: 12-28-2011 20:43 gmt revision:3 [2] [1] [0] [head]

IEEE-4464125 (pdf) Stimulus-Artifact Elimination in a Multi-Electrode System

  • Stimulate and record on the same electrode within 3ms; record on adjacent electrodes within 500us.
  • Target at MEAs, again.
  • Notes that very small charge mismatches of 1% or less, which is common and acceptable in traditional analog circuit designs, generates an artifact that saturates the neural amp signal chain.
  • for stimulating & recording on the same electrode, the the residual charge must be brought down to 1/1e5 the stimulating charge (or less).
  • paper follows upon {833} -- shared author, Blum -- especially in the idea of using active feedback to cancel artifact charge & associated voltage.
  • target the active feedback for keeping all amplifier out of saturation.
  • vary highpass filter poles during artifact supression (!)
  • bias currents of 1fA on the feedback highpass stage. yikes.

Brown EA, Ross JD, Blum RA, Yoonkey N, Wheeler BC, and DeWeerth SP (2008) Stimulus-Artifact Elimination in a Multi-Electrode System. IEEE TRans. Biomed. Circuit Sys. 2. 10-21

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ref: Jimbo-2003.02 tags: MEA microstimulation artifact supression date: 12-17-2011 01:41 gmt revision:2 [1] [0] [head]

PMID-12665038[0] A system for MEA-based multisite stimulation.

  • stimulate and record the same MEA channel.
  • used voltage-control stimulation.
  • very low leakage current switches, DG202CSE, 100Gohm, Maxim, above. non-mechanical = low vibration.
  • switches switch between stimulator and preamp. obvious.
  • uses active shorting post-stimulation to remove residual charge,
  • uses active sample/hold of the preamplifier while the stimulator is connected to the electrodes.
  • adds stimulation pulse to the initial electrode offset (interesting!)

____References____

[0] Jimbo Y, Kasai N, Torimitsu K, Tateno T, Robinson HP, A system for MEA-based multisite stimulation.IEEE Trans Biomed Eng 50:2, 241-8 (2003 Feb)